In the recent years, remarkable progress has been made in the synthesis and characterization of engineered nanoparticles for imaging and treatment of cancers, resulting in several promising candidates in clinical trials. However, the nano drug delivery field has reached a status quo where investigators try new combinations of nanoparticles and materials without good understanding of biological and immunological barriers, cancer pathology and immunology, and using inappropriate and irrelevant models of the cancer disease. There is a growing sentiment in the field that there is need to revisit the basics and to better understand the integrated biological, pathophysiological and immunological processes for effective translation to nanomedicine design and performance. We propose to organize a workshop ?Mechanisms and Barriers in Nanomedicine? at the Beaver Run Resort and Conference Center, Breckenridge, Colorado in July 2016. The program will be focused on the following aspects: a) interactions at the bio-nano interface; b) immune recognition and toxicity of nanomaterials; c) relevance of mouse models; d) in vivo barriers to nanomedicine; d) new targets in oncology; d) regulatory/industrial hurdles to translation. Leading experts will discuss the integrated roles of systems immunology, protein corona, and tumor and vascular cell biology that modulate nanomedicine retention and functionality in tumors. We set to achieve the following goals: a) to provide an educational, yet critical, forum into integrated biochemical and biological barriers controlling nanoparticle delivery and their functionality; b) to provide an update and a paradigm shift on the strategies to mitigating these problems; c) by conducting open, unrestricted, non-proprietary discussion among senior faculty, young investigators and graduate students, we hope to trigger new ideas and concepts that will move the field forward. The main innovation of the workshop is in providing an open forum for discussing problems with drug delivery and in the focus on biological, immunological and translational aspects of nanotechnology. The R13 grant will be used to establish travel awards for young scientists, graduate students and minorities. The venue has excellent facilities to accommodate people with special needs and disabilities and also families with children.